The effects of dietary linoleic acid on reducing serum cholesterol and atherosclerosis development are nullified by a high-cholesterol diet in male and female apoE-deficient mice.

Linoleic acid (LA) has a two-sided effect with regard to serum cholesterol-lowering and pro-inflammation, although whether this fatty acid reduces serum cholesterol and the development of atherosclerosis under high-cholesterol conditions has yet to be ascertained. In this study, we examine the effects of dietary LA on reducing serum cholesterol and atherosclerosis development under high-cholesterol conditions. Male and female apoE-deficient (ApoE-/-) mice were fed AIN-76-based diets containing 10% SFA and 0·04 % cholesterol, 10% LA and 0·04% low cholesterol (LALC), or 10% LA and 0·1% high cholesterol (LAHC) for 9 weeks. The results revealed significant reduction in serum cholesterol levels and aortic lesions with increasing levels of pro-inflammatory biomarkers (urinary isoprostane and aortic MCP-1 mRNA) in male and female LALC groups compared with those in the SFA groups (P < 0·05). Furthermore, whereas there were significant increases in the serum cholesterol levels and aortic lesions (P < 0·05), there was no difference in aortic MCP-1 mRNA levels in male and female LAHC groups compared with those in the LALC groups. A high-dietary intake of cholesterol eliminated the serum cholesterol-lowering activity of LA but had no significant effect on aortic inflammation in either male or female ApoE-/- mice. The inhibitory effect of LA on arteriosclerosis is cancelled by a high-cholesterol diet due to a direct increase in serum cholesterol levels. Accordingly, serum cholesterol levels might represent a more prominent pathogenic factor than aortic inflammation in promoting the development of atherosclerosis.

Dietary sweet potato (Ipomoea batatas L.) leaf extract attenuates hyperglycaemia by enhancing the secretion of glucagon-like peptide-1 (GLP-1).

'Suioh', a sweet potato (Ipomoea batatas L.) cultivar developed in Japan, has edible leaves and stems. The sweet potato leaves contain polyphenols such as caffeoylquinic acid (CQA) derivatives. It has multiple biological functions and may help to regulate the blood glucose concentration. In this study, we first examined whether sweet potato leaf extract powder (SP) attenuated hyperglycaemia in type 2 diabetic mice. Administration of dietary SP for 5 weeks significantly lowered glycaemia in type 2 diabetic mice. Second, we conducted in vitro experiments, and found that SP and CQA derivatives significantly enhanced glucagon-like peptide-1 (GLP-1) secretion. Third, pre-administration of SP significantly stimulated GLP-1 secretion and was accompanied by enhanced insulin secretion in rats, which resulted in a reduced glycaemic response after glucose injection. These results indicate that oral SP attenuates postprandial hyperglycaemia, possibly through enhancement of GLP-1 secretion.

The isoflavone-rich fraction of the crude extract of the Puerariae flower increases oxygen consumption and BAT UCP1 expression in high-fat diet-fed mice.

Puerariae flower extract (PFE) is a crude extract of the Kudzu flower. Previous studies have shown that PFE supplementation exerts anti-obesity and anti-fatty liver effects in high-fat diet-fed mice. In this study, we aimed to identify the PFE components responsible for these effects and to determine their influence on energy expenditure and uncoupling protein 1 (UCP1) expression. Experiments were conducted on C57BL/6J male mice classified into 3 groups: (1) high-fat diet-fed (HFD), (2) high-fat diet-fed given PFE (HFD + PFE), and (3) high-fat diet-fed given the PFE isoflavone-rich fraction (HFD + ISOF). All groups were fed for 42 days. The HFD + PFE and HFD + ISOF groups showed significant resistance to increases in body weight, hepatic triglyceride level, and visceral fat compared to the HFD group. These groups also exhibited significant increases in oxygen consumption and UCP1-positive brown adipose tissue (BAT) area. Our results demonstrate that the active ingredients in PFE are present in the ISOF and that these compounds may increase energy expenditure by upregulation of BAT UCP1 expression. These findings provide valuable information regarding the anti-obesity effects of isoflavones.

The crude extract from puerariae flower exerts antiobesity and antifatty liver effects in high-fat diet-induced obese mice.

Kudzu, a leguminous plant, has long been used in folk medicine. In particular, its flowers are used in Japanese and Chinese folk medicine for treating hangovers. We focused on the flower of Kudzu (Puerariae thomsonii), and we previously reported the antiobesity effect of Puerariae thomsonii flower extract (PFE) in humans. In this study, we conducted an animal study to investigate the effect of PFE on visceral fat and hepatic lipid levels in mice with diet-induced obesity. In addition, we focused on gene expression profiles to investigate the antiobesity mechanism of PFE. Male C57BL/6J mice were fed a high-fat diet (HFD) or an HFD supplemented with 5% PFE for 14 days. PFE supplementation significantly reduced body weight and white adipose tissue (WAT) weight. Moreover, in the histological analysis, PFE supplementation improved fatty liver. Hepatic reverse transcription-polymerase chain reaction revealed that PFE supplementation downregulated acetyl-CoA carboxylase expression. For adipose tissue, the expressions of hormone-sensitive lipase in WAT and uncoupling protein 1 in brown adipose tissue (BAT) were significantly upregulated. These results suggest that PFE exerts antiobesity and antifatty liver effects in high-fat diet-induced obese mice through suppressing lipogenesis in the liver, stimulating lipolysis in WAT, and promoting thermogenesis in BAT.

Puerariae flos alleviates metabolic diseases in Western diet-loaded, spontaneously obese type 2 diabetic model mice.

Puerariae flos extract (PFE) has been reported to have many effects, including preventing the development of hangovers, liver protective effects, and an estrogenic effect. In addition, some papers reported that PFE is effective against metabolic diseases, with hypolipidemic and hypoglycemic effects. However, the mechanism underlying such effects remains unclear. For the purpose of clarifying the effect of PFE on metabolic diseases related to the accumulation of visceral fat and to determine the mechanism of such action, TSOD mice, a multifactorial genetic disease animal model that spontaneously develops various metabolic diseases such as obesity and type 2 diabetes, were given a Western diet (WTD) as an environmental factor to prepare a disease model (TSOD-WTD). When TSOD mice were loaded with WTD, it was confirmed that metabolic diseases such as obesity and abnormal glucose/lipid metabolism are aggravated. In contrast, PFE treatment to TSOD-WTD mice was shown to suppress body weight gain and visceral fat accumulation, alleviated the abnormal glucose tolerance and hyperinsulinemia, as well as causing an increase in blood adiponectin. Furthermore, the suppression of liver enlargement was observed in PFE-treated mice, with suppression of fatty degeneration and anti-inflammatory effect. In addition, to clarify the mechanism of the hyperlipidemia-alleviating effects in the liver, we investigated the effect of PFE on the expression of genes involved in cholesterol homeostasis. PFE was associated with a significant increase in gene expression for cholesterol synthesis rate-limiting enzyme HMG-CoA reductase, cholesterol catabolization enzyme Cyp7A1, bile salt export pump adenosine triphosphate-binding cassette transporter B11, and low-density lipoprotein receptor involved in cholesterol uptake. The above results suggest that PFE acts to alleviate the effects of various metabolic diseases based on the accumulation of visceral adipose tissue, including obesity, diabetes, and hyperlipidemia, with the promotion of catabolization/excretion of cholesterol in the liver being a key mechanism of action.

Flavangenol (pine bark extract) and its major component procyanidin B1 enhance fatty acid oxidation in fat-loaded models.

Flavangenol, one of several pine bark extract products, is expected to prevent metabolic diseases with its potent antioxidant effect, its anti-obesity effect and its improvement of insulin sensitivity. In this study, targeting the liver as one of the organs that plays an important role in energy metabolism, Flavangenol was investigated for its effect on non-alcoholic fatty liver disease (NAFLD), its action mechanism and its active ingredients, using in vivo and in vitro experiment systems. Flavangenol suppressed intrahepatic fat accumulation in Western diet-loaded Tsumura Suzuki Obese Diabetes (TSOD) mice, which develop various metabolic diseases. In addition, Flavangenol significantly increased the mRNA expression levels of fatty acid oxidative enzymes (peroxisomal proliferator-activated receptor α, acyl-CoA oxidase, carnitine palmitoyltransferase). In order to investigate the direct effect of Flavangenol on the liver, an in vitro fatty liver model prepared by adding a free fatty acid to human liver cancer cells (HepG2 cells) was used. In this model, Flavangenol significantly suppressed intracellular fat accumulation. Procyanidin B1, one of the major components of Flavangenol, also suppressed fat accumulation and induced mRNA expression of the fatty acid oxidative enzymes. As mentioned above, Flavangenol showed a significant suppressive effect in the NAFLD model, and it was suggested that the molecular mechanism is induction of fatty acid oxidation, with the effect mainly attributed to procyanidin B1.

Preventive effect of Terminalia bellirica on obesity and metabolic disorders in spontaneously obese type 2 diabetic model mice.

Visceral obesity induces insulin resistance and is recognized as an important risk factor for metabolic syndrome (MS). Therefore, inhibition of lipid absorption from the intestine is regarded as an effective way of preventing MS. Terminalia bellirica is extensively used in Ayurvedic medicine in India and neighboring countries, and the fruit of this plant has been reported to have hypoglycemic and hypolipidemic effects. In this study, we investigated the preventive effect of a hot water extract of T. bellirica fruit (TB) on obesity and various metabolic disorders, and explored its molecular mechanisms and active ingredients. TB treatment had a preventive effect on obesity, insulin resistance, and hyperlipidemia in spontaneously obese type 2 diabetic TSOD mice. To clarify the molecular mechanisms of TB in preventing obesity, we investigated the inhibitory effect on lipid absorption. TB suppressed absorption of triacylglycerol in an olive oil loading test (in vivo) and showed a strong inhibitory effect on pancreatic lipase activity (in vitro). Furthermore, a search for the active ingredients in TB revealed that gallic acid is the component primarily responsible for the inhibition of pancreatic lipase activity. Thus, our findings indicate that TB could be useful in preventing MS. The mechanisms probably involve suppression of the absorption of meal-derived lipids mediated by gallic acid.

Preventive effect of pine bark extract (flavangenol) on metabolic disease in Western diet-loaded tsumura suzuki obese diabetes mice.

It is known that the metabolic syndrome has a multi-factorial basis involving both genetic and environmental risk factors. In this study, Tsumura Suzuki Obese Diabetes (TSOD) mice, a mouse model of multi-factorial, hereditary, obese type II diabetes, were given a Western diet (WTD) as an environmental factor to prepare a disease model (TSOD-WTD) and to investigate the preventive effects of Pine bark extract (Flavangenol) against obesity and various features of metabolic disease appearing in this animal model. In contrast to control Tsumura Suzuki Non-obesity (TSNO) mice, TSOD mice were obese and suffered from other metabolic complications. WTD-fed TSOD mice developed additional features such as hyperinsulinemia, abnormal glucose/lipid metabolism and fatty liver. The treatment with Flavangenol had a suppressive effect on increase in body weight and accumulation of visceral and subcutaneous fat, and also showed preventive effects on symptoms related to insulin resistance, abnormal glucose/lipid metabolism and hypertension. Flavangenol also increased the plasma concentration of adiponectin and decreased the plasma concentration of TNF-α. We next investigated the effect of Flavangenol on absorption of meal-derived lipids. Flavangenol suppressed absorption of neutral fat in an olive-oil-loading test (in vivo) and showed an inhibitory effect on pancreatic lipase (in vitro). The above results suggest that Flavangenol has a preventive effect on severe metabolic disease due to multiple causes that involve both genetic and environmental risk factors. The mechanism of action might involve a partial suppressive effect of meal-derived lipids on absorption.

Linoleic acid-rich fats reduce atherosclerosis development beyond its oxidative and inflammatory stress-increasing effect in apolipoprotein E-deficient mice in comparison with saturated fatty acid-rich fats.

The relative benefit of replacing saturated fatty acid with linoleic acids is still being debated because a linoleic acid-enriched diet increases oxidative and inflammatory stresses, although it is associated with a reduction in serum cholesterol levels. The present study was conducted to evaluate the effect of dietary supplementation of linoleic acid-rich (HL) fat, compared with a saturated fatty acid-rich (SF) fat on atherosclerotic lesion areas, serum and liver cholesterol levels, oxidative stress (urinary isoprostanes and serum malondialdehayde) and inflammatory stress (expression of aortic monocyte chemoattractant protein-1; MCP-1) in apo E-deficient mice. Male and female apo E-deficient mice (8 weeks old; seven to eight per group) were fed an AIN-76-based diet containing SF fat (50 g palm oil and 50 g lard/kg) or HL fat (100 g high-linoleic safflower-seed oil/kg) for 9 weeks. Compared with the SF diet, the HL diet lowered atherosclerosis (P<0.05). It reduced serum total cholesterol levels (P<0.05), increased HDL-cholesterol levels (P<0.05) and lowered liver esterified cholesterol levels (P<0.01). The HL diet-fed mice showed increased expression of MCP-1 mRNA (P<0.05), serum levels of malondialdehayde (P<0.05) and urinary excretion of 2,3-dinor-5,6-dihydro-8-iso-prostaglandin F2alpha; P<0.05). These results suggest that having biomarkers in vivo for oxidative stress and inflammatory status of endothelial cells does not necessarily indicate predisposition to an increased lesion area in the aortic root in apo E-deficient mice fed an HL or SF diet.